1. Field of the Invention
Human lung carcinomas are responsible for most deaths from cancer among men and are in the process of overtaking breast carcinomas as the most frequent cause of cancer death among women (Cancer Facts and Figures, 1983). This disease can be divided into 4 major histological types, i.e., epidermoid (30%), adenocarcinoma (35%), large-cell undifferentiated (15%), and small-cell (20%). Most cases of lung carcinomas are incurable by chemotherapy and radiation therapy. Small cell lung carcinomas may respond to chemotherapy and radiation therapy by a reduction in size, but not a total cure. Complete surgical removal of the tumor appears to be the only effective therapy. Unfortunately, however, fewer than 30% of lung cancer patients have tumors which can be totally resected at diagnosis and of these, fewer than one-third survive 5 years after apparent complete surgical removal of all tumor. There is a great need, therefore, for methods that would make possible an earlier diagnosis of lung cancer, a better definition of the degree of cancer spread, and a more effective therapy.
Monoclonal antibodies may be used for all these purposes. A prerequisite, however, is to find antibodies to antigens that are more strongly expressed in lung cancer than in normal adult tissues. In view of the known heterogeneity of tumor cell populations, the presence of several determinants on the same antigen molecule, the anticipated differences between antigens with respect to their suitability as diagnostic markers as compared to therapeutic targets, and the different biological characteristics of different antibodies to the same antigen, a number of different antibodies may be needed.
2. Description of the Prior Art
Human monoclonal antibodies to lung cancer antigens are described by Sikora et al., Br. J. Cancer (1981) 43: 696-700. Monoclonal antibodies that demonstrate specificity for several types of human lung cancer are disclosed by Cuttitta et al., Proc. Natl. Acad. Sci. U.S.A. (1981) 78: 4591-4595. Antigens associated with a human lung adenocarcinoma defined by monoclonal antibodies are described by Varki et al., Cancer Research (1984) 44: 681-687.
Mouse monoclonal antibodies to glycolipid Le.sup.x antigens are described by Hakomori et al., in Biochemical and Biophysical Research Communications (1981) 100: 1578-1586; Brockhaus et al., Arch. Biochem. Biophys. (1982) 217: 647; Fukushi et al., J. Biol. Chem. (1984) 259: 506; Fukushi et al. J. Exp. Med. (1984) 159: 506; Chia et al., Cancer Res. (1985) 45: 435. Antibodies to Le.sup.y antigens have been described by Abe et al., J. Biol. Chem (1983) 258: 8934; Lloyd et al., Immunogenetics (1983) 17: 537; Brown et al., Biosci. Rep. (1983) 3: 163.
Continuous cultures of fused cells secreting antibody of predefined specificity are described by Kohler et al., Nature (1975) 265: 495-497.